Chronic Inflammation Flashcards
What happens when wound healing progresses nicely ?
have resolution and then go back to homeostasis which will then restore normal function
What is resolution?
- clearance of injurious stimuli
- clearance of mediators and acute inflammatory cells
- replacement of injured cells
- normal function
What happens if initial cause of acute inflammation persists and can’t be healed or eradicated by neutraphils and macrophages ?
we then process into chronic inflammation
What can happen at the same time as chronic inflammation ?
healing
What are the causes of chronic inflammation ?
- Persistent infections (viral, fungal, resistant bacteria) - not killed off and continue to affect healthy cells causing cellular death
- Prolonged exposure to a toxin/foreign object
- Exogenous, e.g. asbestosis- e.g splinter- easy to remove - which allows acute inflammation to continue and will trigger wound repair
- Endogenous (within you) , e.g. atherosclerosis (plasma lipids)- accumulation of fat which build up in arteriole walls- narrow the diamter of blood vessels- increase strokes and heart attack - hard to get rid of- continuous toxin - chronic inflammation surrounding these plaques
- Immune mediated
- Autoimmune disease, immune response against hosts’ own antigens.
e. g. Multiple sclerosis, Rheumatoid arthritis, Graves’ disease
- immune system identifies this as being foreign cells although they are your own cells and triggers immune response to kill these cells which trigger inflammation and wound repair
- however new cells being produced to repair the area - would be seen as foreign - as same identity of the cells that were attacked by own immune system- then will kill off- pepertual cycle of inflammation and repair- Chronic inflammation
-Unregulated immune response to an antigen e.g. Asthma (environmental trigger) or IBS (bacterial)
What is chronic inflammation ?
inflammation of prolonged duration i.e weeks to months even years
-Chronic inflammation is unregulated injury/repair in a perpetual cycle.
What are the 3 processes chronic inflammation is characterised by ?
-3 processes occur simultaneously
- Active inflammation - invasion / Infiltration by mononuclear cells : these cells then differentiate into macrophages, lymphocytes, plasma cells
- B cells - which are differentiated and matured into plasma cells - now can secrete antibodies- plasma cells are differentiated B-lymphocytes. They are white blood cells that secrete large volumes of antibodies.
- Tissue destruction : induced by persistent injurious agent or by inflammatory cells
more cells go into necrosis
- this persistent long episode of cell death then induces more active infalmmation of the site- which leads back to more leukocytes being attracted and stimulated in the area- so got continue tissue destruction - which means tissue destruction triggers active inflammation therefore attempts at repair - Attempts at repair/healing :
- connective tissue replacement of damaged tissue
- mainly by angiogenesis and fibrosis (scarring)
- more cells produced by mitosis so more cells to be destroyed again :(
What does tissue destruction trigger ?
active inflammation therefore more wound healing response /repair
What are the key players of chronic inflammation?
macrophages
What do the macrophages do in chronic inflammation ?
at the end off acute inflammation you get recruitment of monocytes from peripheral vasculature through leukocyte extravastjion
- when they enter tissues they differentiate into macrophages
- if neutrophils done their job and neutralised all the causes of acute inflammation then the macrophages come in and see the area is clear and there is no other inducers of inflammation and so the macrophages start to secrete the factors which will induce wound repair
- however if they come into this environment and still see a problem such as a bacterial infection - then inestad of inducing wound repair they tart to become phagocytic and will phagocytose bacteria infected cells or signal other leukocytes that the inflammation must continue so start to do same job as neutrophils which result in more tissue damage
What else do the macrophages do ?
- can be activated by T c ells or cytokines
- they induce tissue repair
- If stimulus persists they also respond to tissue injury and induce more inflammation - which leads to a form of wound healing terms fibrosis - because got excess of wound repair going on which gets destroyed .
What do macrophages do ?
- Dominant cell in chronic inflammation
- Part of mononuclear phagocyte system
- Derive from blood monocytes
What is fibrosis ?
excess of wound healing under these destructive conditions
-as more tissue is being generated it can also be destroyed again - excessive cycle of wound repair - leads to dense matter of tissues - fibrotic tissue
What are the 2 distinct type of macrophages ?
M1 = Destroyers – clear up injury site- phagocytose site M2 = Healers – induce repair and wound healing - secrete factors to induce wound repair
-this depends on which cytokine it is exposed to in the environment - if concentration of cytokine changes the macrophage can change its phase (from m1 or m2)
What happens when cytokines Interleukins (IL13, IL4) are secreted ino environment ?
promote M2 healer phase
- induce macrophage to promote wound repair
- can secrete anti-inflammatory singles which can suppress any localised inflammatory responses going on
